The role of interferon-alpha in the regulation of sleep

Summary

Interferon-alpha (IFN-alpha) exerts strong antiviral effects and was among the first cytokines suspected to contribute to alterations of sleep during infectious challenge. A short review of the relevant literature is provided. Administration of IFN-alpha in rabbits increased body temperature and, in parallel, slow wave sleep (SWS). These findings were taken to suggest a sleep promoting effect of the cytokine. However, experiments in monkeys, although indicating increased behavioral signs of fatigue, did not reveal changes towards enhanced sleep after IFN-alpha. In cancer patients treated with high doses of IFN-alpha enhanced fatigue is commonly observed. We conducted a first study in healthy young men, evaluating the effects of IFN-alpha given at a fairly low dose (1000 and 10,000 IU/kg body weight, subcutaneously) on nocturnal sleep. The cytokine was administered subcutaneously at 19.00h prior to sleep. It distinctly reduced SWS during the early night and, at the high dose, REM sleep across the entire night. Effects on sleep were accompanied by increased feelings of tiredness, increased pituitary-adrenal secretory activity, increased growth hormone secretion and increased IL-6 plasma concentrations. Body temperature remained almost unchanged. These results support an acute disrupting effect of IFN-alpha on nocturnal sleep in humans. Similar disruptive effects have been observed in previous studies after administration of IL-6 in healthy humans. Together, the data support the view that enhanced release of proinflammatory cytokines in humans acutely impairs sleep. Given that the pattern of changes after IFN-alpha and also after IL-6 is in some of its essential features is reminiscent of the symptoms seen in depressed patients, a contribution of host defense mechanisms to this disease and associated sleep disruption should be taken into consideration.